Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery

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Oikari , L E , Pandit , R , Stewart , R , Cuní-López , C , Quek , H , Sutharsan , R , Rantanen , L M , Oksanen , M , Lehtonen , S , de Boer , C M , Polo , J M , Götz , J , Koistinaho , J & White , A R 2020 , ' Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery ' , Stem cell reports , vol. 14 , no. 5 , pp. 924-939 . https://doi.org/10.1016/j.stemcr.2020.03.011

Title: Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery
Author: Oikari, Lotta E.; Pandit, Rucha; Stewart, Romal; Cuní-López, Carla; Quek, Hazel; Sutharsan, Ratneswary; Rantanen, Laura M.; Oksanen, Minna; Lehtonen, Sarka; de Boer, Carmela Maria; Polo, Jose M.; Götz, Jürgen; Koistinaho, Jari; White, Anthony R.
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2020-05-12
Language: eng
Number of pages: 16
Belongs to series: Stem cell reports
ISSN: 2213-6711
URI: http://hdl.handle.net/10138/316152
Abstract: The blood-brain barrier (BBB) presents a barrier for circulating factors, but simultaneously challenges drug delivery. How the BBB is altered in Alzheimer disease (AD) is not fully understood. To facilitate this analysis, we derived brain endothelial cells (iBECs) from human induced pluripotent stem cells (hiPSCs) of several patients carrying the familial AD PSEN1 mutation. We demonstrate that, compared with isogenic PSEN1 corrected and control iBECs, AD-iBECs exhibit altered tight and adherens junction protein expression as well as efflux properties. Furthermore, by applying focused ultrasound (FUS) that transiently opens the BBB and achieves multiple therapeutic effects in AD mouse models, we found an altered permeability to 3-5 kDa dextran as a model cargo and the amyloid-beta (A beta) peptide in AD-iBECs compared with control iBECs. This presents human-derived in vitro models of the BBB as a valuable tool to understand its role and properties in a disease context, with possible implications for drug delivery.
Subject: 3112 Neurosciences
Alzheimer disease
endothelial cells
blood-brain barrier
tight junctions
ultrasound therapy
induced pluripotent stem cells
induced brain endothelial cells
focused ultrasound
DEPOSITION
SCANNING ULTRASOUND
BARRIER
BETA-PEPTIDE
PATHOLOGY
ULTRASOUND TREATMENT
P-GLYCOPROTEIN
DISEASE
BLOOD-BRAIN
EXPRESSION
1182 Biochemistry, cell and molecular biology
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